jacob_cannell comments on Rationality Case Study - Ad-36 - Less Wrong

22 Post author: Perplexed 22 September 2010 06:32PM

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Comment author: Jonathan_Graehl 22 September 2010 08:16:16PM 4 points [-]

Criticisms of the recent Gabbert et al AD36<->obesity paper:

The data indicated that for the AD36 Negative group, the ages were 8-11 yrs (18%), 12-15 yrs (65%), and 15-18 yrs (17%). For the AD36 Positive group, the ages were 8-11 yrs (5%), 12-15 yrs (32%), and 15-18 yrs (63%). This is as we surmised above: more older kids are in the AD36 group. The weight average for the AD36 Negative group was 69 kg (+/- 24 kg SD); for the AD36 Positive group is was 93 kg (+/- 24 kg SD).

Thus, one sure finding is that older kids are heavier: in fact, they were about 24 kg heavier, which translated to about 50 lbs. It is at least good to see that the press release got this figure correct.

Another finding is that older kids are more likely to have been previously infected by AD36, also as we surmised (in two years, you have have plenty of colds).

There is no modeling of the expected distribution of biometric properties of the two populations (AD36-negative and -positive) given the other statistics (age,sex,race) reported. This is extremely surprising to me.

However, it's not just that older kids (adults, really) weigh more - the size-relative metrics BMI, and waist/height ratio were also higher in the AD36 antibody group. But still, those should be adjusted for age as well; their distribution (and mean) will surely change with age, and definitely will change for the worse with age in the destined-to-be-obese (it takes time to blossom into full adult obesity). The fact that no such adjustment was made means that the study contributes almost no additional evidence, but this could be corrected with a proper analysis. And, supposing the raw data is available, this can happen.

The two populations also have a significant sex difference: the AD36-negative group is 58% male, and the AD36-positive is only 47%. However, it looks like adult men and women have similar recommended BMI and waist/height ratios (actually, women are recommended to have slightly lower) - I don't know what the actual averages are. Racially, there's a 13% shift from "non-hispanic white" to "hispanic" in the AD36-positive population. While I don't know how different those groups are re: AD36-positivity or BMI etc., this should be considered as well. The age mismatch is definitely the most severe problem.

The "discussion" section lists much other work which seems to provide better evidence of a AD36-obesity link (I assume the authors are leaving out any negative results that don't support their views). For example:

[In] a small substudy of adult twins with discordant AD36-specific antibody status, 13 Twins with antibodies to AD36 were noted to have higher BMI values and greater proportions of body fat then their respective antibody-negative twins.

(evidence of correlation, not causality - would be quite strong evidence if the number of twins and BMI/body fat mismatch were large enough)

infection of nonhuman primates, rodents, and chickens with AD36 increased total body fat independent of energy intake

(causality in animal models, although i would hope for exposure rather than infection as the trigger - perhaps p(infection|exposure) is high enough that it doesn't matter)

adipose-derived stem/stromal cells ... infected with AD36 showed increased differentiation and higher levels of lipid accumulation than noninfected control cells

(causal, but in vitro: doesn't guarantee net fattening in the context of a human body)

Comment author: jacob_cannell 22 September 2010 08:55:18PM 1 point [-]

infection of nonhuman primates, rodents, and chickens with AD36 increased total body fat independent of energy intake

(causality in animal models, although i would hope for exposure rather than infection as the trigger - perhaps p(infection|exposure) is high enough that it doesn't matter)

This wasn't clear to me - isn't infection more specific than exposure? I mean presumably only infection would hae metabolic effects, and exposure doesn't always result in infection

Comment author: Jonathan_Graehl 22 September 2010 11:06:02PM 3 points [-]

The causal intervention is really an act of exposure.

If you expose once, or expose until infected, or expose but exclude those not infected, then the difference between infected and not-infected populations is obscured; the reason some individuals were infected (or not) from a single exposure needs to be explained. If it isn't, then I can say that part of any difference between the infected and not-infected populations is due to whatever factor made some of them fall prey to the infection on one exposure.

Comment author: jacob_cannell 22 September 2010 11:08:06PM 0 points [-]

Ah right, I see.